Omeprazole, i.e. the compound 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole, and therapeutically acceptable salts thereof, are described in EP 5129. Some specific alkaline salts of omeprazole are disclosed in EP 124 495.
Omeprazole is a sulfoxide and a chiral compound, wherein the sulfur atom is the stereogenic center. Thus, omeprazole is a racemic mixture of its two single enantiomers, the R— and S-enantiomer of omeprazole, the latter having the generic name esomeprazole. Esomeprazole is recently launched as a new generation of proton pump inhibitors, wherein the active pharmaceutical ingredient is esomeprazole magnesium salt. Esomeprazole shows improvements in the treatment of GERD compared to previous medications.
The absolute configurations of the enantiomers of omeprazole have been determined by an X-ray study of an N-alkylated derivative of the (+)-enantiomer in non-salt form. The (+)-enantiomer of the non-salt form and the (−)-enantiomer of the non-salt form were found to have R and S configuration, respectively, and the (+)-enantiomer of the magnesium salt and the (−)-enantiomer of the magnesium salt were also found to have R and S configuration, respectively. The conditions for the optical rotation measurement for each of these enantiomers are described in WO 94/27988.
Certain salts of single enantiomers of omeprazole and their preparation are disclosed in WO 94/27988. These compounds have improved pharmacokinetic and metabolic properties, which will give an improved therapeutic profile such as a lower degree of interindividual variation.
WO 96/02535 discloses a process for the preparation of the single enantiomers of omeprazole and salts thereof, including a sodium salt.
WO 98/54171 discloses a process for the preparation of the magnesium salt of the S-enantiomer of omeprazole trihydrate, wherein a potassium salt of S-omeprazole is used as an intermediate.
WO 00/44744 discloses a potassium salt of S-omeprazole free from methanol. WO 03/089408 (Sun Pharmaceutical Industries Limited) discloses alkali or alkaline earth metal salts of esomeprazole, including a sodium salt.